Comparison of Effect Sizes Associated With Biomarkers Reported in Highly Cited Individual Articles and in Subsequent Meta-analyses

[Eugene Garfield]

Comparison of Effect Sizes Associated With Biomarkers Reported in Highly Cited 
Individual Articles and in Subsequent Meta-analyses

Author(s): Ioannidis, JPA (Ioannidis, John P. A.); Panagiotou, OA (Panagiotou, 
Orestis A.)
Source: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION  Volume: 
305  Issue: 21  Pages: 2200-2210  Published: JUN 1 2011  

Abstract: Context Many biomarkers are proposed in highly cited studies as 
determinants of disease risk, prognosis, or response to treatment, but few 
eventually transform clinical practice. 
Objective To examine whether the magnitude of the effect sizes of biomarkers 
proposed in highly cited studies is accurate or overestimated. 
Data Sources We searched ISI Web of Science and MEDLINE until December 
2010. 
Study Selection We included biomarker studies that had a relative risk 
presented in their abstract. Eligible articles were those that had received more 
than 400 citations in the ISI Web of Science and that had been published in 
any of 24 highly cited biomedical journals. We also searched MEDLINE for 
subsequent meta-analyses on the same associations (same biomarker and same 
outcome). 
Data Extraction In the highly cited studies, data extraction was focused on the 
disease/outcome, biomarker under study, and first reported relative risk in the 
abstract. From each meta-analysis, we extracted the overall relative risk and 
the relative risk in the largest study. Data extraction was performed 
independently by 2 investigators. 
Results We evaluated 35 highly cited associations. For 30 of the 35 (86%), the 
highly cited studies had a stronger effect estimate than the largest study; for 
3 the largest study was also the highly cited study; and only twice was the 
effect size estimate stronger in the largest than in the highly cited study. For 
29 of the 35 (83%) highly cited studies, the corresponding meta-analysis found 
a smaller effect estimate. Only 15 of the associations were nominally 
statistically significant based on the largest studies, and of those only 7 had a 
relative risk point estimate greater than 1.37. 
Conclusion Highly cited biomarker studies often report larger effect estimates 
for postulated associations than are reported in subsequent meta-analyses 
evaluating the same associations. JAMA. 2011;305(21):2200-2210 
www.jama.com
Language: English
Document Type: Review

KeyWords Plus: CORONARY-HEART-DISEASE; HELICOBACTER-PYLORI 
INFECTION; PROSTATE-CANCER RISK; C-REACTIVE PROTEIN; GROWTH-
FACTOR-I; PLATELET GLYCOPROTEIN RECEPTOR; TYPE-2 DIABETES-MELLITUS; 
LYMPHOTOXIN-ALPHA GENE; BREAST-CANCER; MYOCARDIAL-INFARCTION

Addresses: [Ioannidis, JPA] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, 
Stanford, CA 94305 USA
[Ioannidis, JPA] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 
94305 USA
[Ioannidis, JPA; Panagiotou, OA] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, 
Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece
Reprint Address: Ioannidis, JPA (reprint author), Stanford Univ, Sch Med, 
Stanford Prevent Res Ctr, Med Sch Off Bldg,Room X306,251 Campus Dr, 
Stanford, CA 94305 USA

E-mail Address: jioannid at stanford.edu
ISSN: 0098-7484
URL: http://jama.ama-assn.org/content/305/21/2200